Apoptosis or programmed cell death is a major regulator of embryonic development. The development of hematopoietic cells requires a delicate balance between proliferation and apoptosis that is regulated in part by hematopoietic cytokines. Apoptosis plays a critical role in controlling the number of cells and eliminating cells that are no longer needed or are seriously damaged. Forkhead FOXO transcription factors are key regulators of programmed cell death in cytokine deprived hematopoietic cells. These highly conserved transcription factors, are involved in many fundamental biological responses in addition to the regulation of apoptosis. Importantly, FOXO transcription factors have also been identified at the sites of chromosomal rearrangements in certain human tumors and leukemias. Despite their apoptotic role as a result of hematopoietic cytokine deprivation and their dysregulation in leukemia, the function of FOXO transcription factors during normal development of blood forming cells is not known. These studies are aimed at investigating the expression and the function of these proteins and their potential involvement in the onset and development of the hematopoietic system using the mouse embryonic stem cell system.